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How does cancer respond and resist pd-1 blockade therapy?

Prof. Antoni Ribas, will reveal his findings on this question during ISCORT Congress 2020

Antoni Ribas, M.D., Ph.D.
University of California Los Angeles (UCLA) >>

  • Elected president of AACR 2019-2020
  • Chair of the Melanoma Committee at SWOG
  • Director of the Tumor Immunology Program at JCCC
Jan 8th

Jan 8th

Antoni Ribas lecture at ISCORT congress

Jan 8th 01/08/2020 12:10 PM 01/08/2020 12:40 PM at ISCORT congress THE SCIENCE OF CANCER IMMUNOTHERAPY at ISCORT congress

12:10 PM

THE SCIENCE OF CANCER IMMUNOTHERAPY

Jan 8th 01/08/2020 01:25 PM 01/08/2020 02:00 PM ISCORT congress RESISTANCE TO IMMUNOTHERAPY at ISCORT congress

13:25 PM

RESISTANCE TO IMMUNOTHERAPY

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Antoni Ribas, M.D., Ph.D.

Cutting-edge treatments

Ribas is conducting several clinical trials of cutting-edge treatments including both immunotherapies and targeted stem cell-based therapies. In 2017, he launched a first-of-its-kind trial that involves genetically engineering blood-forming stem cells to produce cancer-fighting T cells to treat melanomas and sarcomas and later multiple myeloma. The clinical trial involves a dual approach intended to provide patients with both short and long-term immune responses to their cancer. This is accomplished by giving patients modified blood-forming stem cells and modified mature T cells in a single transplant. Upon transplant, the modified mature T cells begin fighting the cancer immediately, while the modified blood-forming stem cells work to generate an on-going supply of new modified T cells, resulting in a lasting immune response to the cancer1. Ribas is also leading clinical trails in the field of Nanoparticle-siRNA therapeutics2.

1Chao Ma, Ann F Cheung, Thinle Chodon, Richard C Koya, Zhongqi Wu, Charles Ng, Owen N. Witte, David Baltimore, Bartosz Chmielowski, James S. Economou, Begonya Comin-Anduix, Antoni Ribas*, James R. Heath*. Multifunctional T-cell analyses to study response and progression in adoptive cell transfer immunotherapy. *equal contribution as corresponding and senior authors. Cancer Discovery 2013 Apr; 3 (4): 418-29.
2Mark E. Davis, Jonathan E. Zuckerman, Chung Hang J. Choi, David Seligson, Anthony Tolcher, Christopher A. Alabi, Yun Yen, Jeremy D. Heidel, Antoni Ribas. Evidence of RNAi in humans from systemically administered siRNA via targeted nanoparticles. Nature 2010 Apr 15; 464 (7291): 1067-70.
Antoni Ribas, M.D., Ph.D.

Resistance strategies

Ribas studies how the immune system responds to and develops resistance to immunotherapies, and how combination therapies may be used to overcome treatment resistance. One such treatment the Ribas lab is evaluating combines pembrolizumab with a targeted therapy that blocks a protein that leads to mutations in the BRAF gene.The BRAF gene makes a protein called B-RAF, which is involved in cell communication and growth. When BRAF genes are mutated, they can increase the growth and spread of cancer cells; approximately one‐half of all patients with melanoma have mutations in the BRAF gene3-5*.

* The BRAF gene makes a protein called B-RAF, which is involved in cell communication and growth. When BRAF genes are mutated, they can increase the growth and spread of cancer cells; approximately one‐half of all patients with melanoma have mutations in the BRAF gene.
3 Caroline Robert*, Antoni Ribas*, Jedd D. Wolchok, F. Stephen Hodi, Omid Hamid, Richard Kefford, Jeffrey S. Weber, Anthony M. Joshua, Wen-Jen Hwu, Tara C. Gangadhar, Amita Patnaik, Roxana Dronca, Hassane Zarour, Richard W. Joseph, Peter Boasberg, Bartosz Chmielowski, Christine Mateus, Michael A. Postow, Kevin Gergich, Jeroen Elassaiss-Schaap, Xiaoyun (Nicole) Li, Robert Iannone, Scot W. Ebbinghaus, S. Peter Kang, Adil Daud. *equal contribution. Anti–PD-1 Treatment with MK-3475 in Ipilimumab-Refractory Advanced Melanoma. The Lancet 2014 Sep 20; 384 (9948): 1109-17.
4 Ramin Nazarian, Hubing Shi, Qi Wang, Xiangju Kong, Richard C. Koya, Hane Lee, Zugen Chen, Mi-Kyung Lee, Narsis Attar, Hooman Sazegar, Thinle Chodon, Stanley F. Nelson, Grant A. McArthur, Jeffrey A. Sosman, Antoni Ribas, Roger S. Lo. Melanomas acquire resistance to V600EB-RAF inhibition by RTK upregulation or N-RAS mutation. Nature 2010; Dec 16; 468 (7326): 973-7.
5 Antoni Ribas, Rene Gonzalez, Anna Pavlick, Omid Hamid, Thomas F. Gajewski, Igor Puzanov, Adil Daud, Lawrence Flaherty, Theodore Logan, Bartosz Chmielowski, Karl Lewis, Damien Kee, Peter Boasberg, Ming Yin, Iris Chan, Nicholas Choong, Grant McArthur. Combination of the BRAF inhibitor vemurafenib and the MEK inhibitor cobimetinib in patients with advanced BRAFV600- mutated melanoma. The Lancet Oncology 2014 Aug; 15 (9): 954-65.
Antoni Ribas, M.D., Ph.D.

Molecular imaging and advanced monitoring

Ribas and his team utilize molecular imaging technology such as PET scans to investigate and understand precisely how novel immunotherapies work on a molecular level. They aim to use these technologies to guide and evaluate new therapeutic strategies for melanoma6,7.

6 Escuin-Ordinas H, Elliott MW, Atefi M, Lee M, Ng C, Wei L, Comin-Anduix B, Montecino-Rodriguez E, Avramis E, Radu C, Sharp LL, Ribas A. PET imaging to non-invasively study immune activation leading to antitumor responses with a 4-1BB agonistic antibody. J Immunother Cancer. 2013 Aug 27;1:14.
7 Thinle Chodon, Begoña Comin-Anduix, Bartosz Chmielowski, Richard C. Koya, Zhongqi Wu, Martin Auerbach, Charles Ng, Earl Avramis, Elizabeth Seja, Arturo Villanueva, Tara A. McCannel, Akira Ishiyama, Johannes Czernin, Caius G. Radu, Xiaoyan Wang, David W. Gjertson, Alistair J. Cochran, Kenneth Cornetta, Deborah J.L. Wong, Paula Kaplan-Lefko, Omid Hamid, Wolfram Samlowski, Peter A. Cohen, Gregory A. Daniels, Bijay Mukherji, Lili Yang, Jerome A. Zack, Donald B. Kohn, James R. Heath, John A. Glaspy, Owen N. Witte, David Baltimore, James S. Economou and Antoni Ribas. Adoptive Transfer of MART-1 T-Cell Receptor Transgenic Lymphocytes and Dendritic Cell Vaccination in Patients with Metastatic Melanoma. Clinical cancer research. 2014 May; 20 (9)
Antoni Ribas, M.D., Ph.D.

Leadership in the development of new cancer I-Os

Antoni Ribas has been awarded the sixth American Association of Cancer Research–Cancer Research Institute Lloyd J. Old Award in Cancer Immunology. Dr. Ribas is being recognized for his leadership in the development of new cancer immunotherapies. His research has been aimed at gaining a better understanding of immunotherapies to treat cancer with reduced toxicity for patients with melanoma. He led the clinical program that demonstrated the effectiveness of pembrolizumab (Keytruda).